Filaggrin-2 (FLG2)
The protein contains 2391 amino acids for an estimated molecular weight of 248073 Da.
Essential for normal cell-cell adhesion in the cornified cell layers (PubMed:29758285). Important for proper integrity and mechanical strength of the stratum corneum of the epidermis (PubMed:29505760). (updated: Feb. 13, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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No binding partner found
Biological Process
Cell adhesion
Epidermis morphogenesis
Establishment of skin barrier
Neutrophil degranulation
The reference OMIM entry for this protein is 616284
Filaggrin family member 2; flg2
Filaggrin 2
Ifapsoriasin; ifps
DESCRIPTION
The FLG2 gene encodes a member of the S100 fused-type protein (SFTP) family. These proteins are essential components that maintain epithelial homeostasis and barrier function (summary by Wu et al., 2009).CLONING
By database analysis, exon sequencing, 5-prime and 3-prime RACE, and short-range overlapping PCR with human foreskin-derived primary keratinocytes, Wu et al. (2009) cloned FLG2. The deduced 2,391-amino acid protein has an N-terminal S100 (see S100A1, 176940)-type calcium-binding domain, followed by an EF-hand domain, and central A-type and B-type repetitive regions before the C-terminus. The A-type repetitive region is similar to repeats found in hornerin (HRNR; 616293), with 9 repeats of 75 to 77 amino acids each, and regularly spaced phe, ser, and thr residues. The B-type repeat region has 14 repeats of 75 to 77 amino acids each, similar to the repeats found in filaggrin (FLG; 135940). The FLG-like repeats lack phe residues but are rich in his and arg residues. RT-PCR detected FLG2 expression in skin, thymus, stomach, tonsils, testis, and placenta, but not in other tissues examined. Quantitative RT-PCR detected FLG2 in skin samples from all human body regions examined. Immunohistochemical and immunoelectron microscopy detected FLG2 in the upper epidermal layers of skin, with FLG2 localized throughout the cytoplasm in the stratum corneum layer and in keratohyalin granules of various sizes in the stratum granulosum layer. Western blot analysis of epidermal extracts detected 2 strong bands: one corresponding to the expected 248-kD molecular mass of full-length FLG2, and the other corresponding to a fragment of approximately 65 kD. Smaller-sized FLG2 bands were detected in stratum corneum extracts, including a prominent band of approximately 15 kD, suggesting proteolytic processing during maturation of skin, similar to that found with filaggrin. By differential extraction, Western blot analysis, and confocal microscopic analysis of normal human epidermis, Hsu et al. (2011) detected full-length FLG2 in the cytoplasm of the upper granular keratinocyte layer, where it showed a granular distribution that suggested storage of FLG2 in keratohyalin granules. Smaller processed FLG2 proteins and peptides were detected in the matrix of the lower corneocyte layer, but not in the upper corneocytes.GENE FUNCTION
Using RT-PCR, Wu et al. (2009) found that expression of both FLG and FLG2 increased 200-fold in cultured human foreskin keratinocytes following calcium-induced differentiation. Using Western blot analysis and mass spectrometry, Hsu et al. (2011) found that calpain-1 (CAPN1; 114220) progressively hydrolyzed an epitope-tagged human FLG2 fragment corresponding to B-repeats B7 to B10, giving a ladder-like appearance to cleavage products. Calcium was required for the reaction. Deimination of arginines near the CAPN1 cleavage sites by human peptidylarginine deiminases (see PADI1, 607934) enhanced CAPN1-dependent processing of the B-repeats. FLG2 and CAPN1 colocalized in the cytoplasm of granular keratinocytes and lower corneocytes, suggesting a role for CAPN1 in FLG2 processing. In mice overexpressing the Capn1 inhibitor calpastatin (CAST; 114090), Flg2 processing in epidermis was delayed. CAPN1-sensitive sites were not found in the A-type repeats of FLG2, suggesting that other proteases are involved in FLG2 processing in skin.GENE STRUCTURE
Wu et al. (2009) determined that the FLG2 ... More on the omim web site
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616284 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated